Immune Biomarker Study for Head and Neck Cancer

NCT05375266 | Recruiting

• 1 other identifier: 12-384-B
• Study Type: observational
• Target: 1,100
• Locations: 1 country
• Sites: 3

Brief Summary

The aim of this prospective non-interventional multi-center trial is to study the prognostic value of intratumoral and systemic immune biomarkers in newly diagnosed non-metastatic head and neck cancer. Furthermore, the local immunological processes in the tumor will be correlated with the systemic immune status determined in the peripheral blood to identify prognostic immune signatures. In addition, tumor organoids will be generated ex vivo for functional biological analyses. The main objective is to create a prognostic score determined by clusters based on tumor immunologic criteria.

Conditions

Head and Neck Cancer; Oral Cavity Cancer; Oropharyngeal Cancer; Hypopharyngeal Cancer; Laryngeal Cancer

Keywords

Immunologic markers; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Observation of changes in an established immune matrix (intratumoral and systemic) of responding/non-responding patients at certain points in time in the course of treatment

  Based on the intrinsic immunological biology of the tumors, different immune cells and tumor cell markers will characterize immunological groups using cluster analysis. Immune matrix of patients assessed by LIPS (liquid immune profile-based signature) (acc. Zhou et al. JITC 2021) and Tumour Associated Lymphocytes (TAL).

  Change of the immune matrix from baseline (before surgery; day0) and after surgery (day 7) and at the end of radiotherapy (day 60-70) and end of study period up to 5 years

Secondary Outcomes (5)

• Longitudinal immunophenotyping of the patients: Detection of about 30 distinct immune cell (sub)types together with their activation markers during study period

  The analyses are conducted at time points before (day 0) surgery and after surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years

• Analysis of cytokines in peripheral blood and their change at certain points in the course of treatment

  The analyses are conducted at time points before (day 0) surgery and after surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years

• Determination of transcription processes in the immune cells at certain points in the course of treatment to extend the prognostic immune signature

  The analyses are conducted at time points before (day 0) surgery and after Surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years

• Analysis of patient's metabolic state

  The analyses are conducted at time points before (day 0) surgery and after Surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years

• Analysis of patient's microbiomic state by examination of saliva, tumor and stool

  The analyses are conducted at time point before surgery (day 0)

Study Arms (2)

Study Cohort

The study cohort consist of patients with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, paranasal sinuses or larynx in stage UICC (Union internationale contre le cancer) II-IVB

Other: Sampling

Control Group

The control group consists of patients with no current diagnoses of cancer undergoing surgery at the participating medical center

Other: Sampling

Interventions

Sampling OTHER

This is an observational study. Consequently, study participation does not alter the therapy of the treated disease. Blood will be drawn from patients at several time points during and after radiotherapy (RT) and therapy with immune checkpoint inhibitor (ICI) for detailed immunomonitoring of the patients. In addition, faeces and sputum of the patients for microbiomic and metabolomic measures will be collected. Whenever possible, adequate tissue samples are taken from the center of the tumor and a biopsy is taken from the edge of the tumor including the adjacent mucosa in the nearby area without affecting the pathological assessment (study group). Blood, faeces and sputum will be taken from patients of the control group prior to surgery. After surgery, only blood will be taken.

Control Group; Study Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients presenting for treatment at the participating study centers and meeting the inclusion criteria

You may qualify if:

• Initial diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, paranasal sinuses or larynx in stage UICC II-IVB (study group)
• Diseases other than malignant diseases (patients with the indication for surgery of the ear, nose nose or maxillofacial surgery) (control group)
• Absence of a currently existing or previous malignant disease regardless of the anatomical localization (control group)
• Agreement of the patients for sampling blood, saliva and stool as well as consent to the preservation of all samples for further study purposes
• Age ≥ 18 years
• Cognitive ability of the patients to understand the meaning and purpose of the study and agree to it

You may not qualify if:

• Carcinomas in which it is (likely) impossible to take a sample without interfering with the further pathological assessment
• Present drug abuse
• Patients who are unable or unwilling to behave and receive treatment according to protocol
• Patients who are legally patronized
• Patients who are not eligible for participation in the study due to language barrier

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead
• University Hospital Erlangen: collaborator
• University Hospital Regensburg: collaborator
• University Hospital Augsburg: collaborator

Study Sites (3)

ENT - Head and Neck Surgery Department

Erlangen, Bavaria, 91054, Germany

RECRUITING

Maxillo-Facial-Surgery Department

Erlangen, Bavaria, 91054, Germany

RECRUITING

Radiation Oncology Department

Erlangen, Bavaria, 91054, Germany

RECRUITING

Related Publications (13)

• O'Sullivan B, Huang SH, Su J, Garden AS, Sturgis EM, Dahlstrom K, Lee N, Riaz N, Pei X, Koyfman SA, Adelstein D, Burkey BB, Friborg J, Kristensen CA, Gothelf AB, Hoebers F, Kremer B, Speel EJ, Bowles DW, Raben D, Karam SD, Yu E, Xu W. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016 Apr;17(4):440-451. doi: 10.1016/S1470-2045(15)00560-4. Epub 2016 Feb 27.

  PMID: 26936027 BACKGROUND

• de Ruiter EJ, Ooft ML, Devriese LA, Willems SM. The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis. Oncoimmunology. 2017 Aug 9;6(11):e1356148. doi: 10.1080/2162402X.2017.1356148. eCollection 2017.

  PMID: 29147608 BACKGROUND

• Hecht M, Gostian AO, Eckstein M, Rutzner S, von der Grun J, Illmer T, Hautmann MG, Klautke G, Laban S, Brunner T, Hinke A, Becker I, Frey B, Semrau S, Geppert CI, Hartmann A, Balermpas P, Budach W, Gaipl US, Iro H, Fietkau R. Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8. J Immunother Cancer. 2020 Oct;8(2):e001378. doi: 10.1136/jitc-2020-001378.

  PMID: 33023982 BACKGROUND

• Wondergem NE, Nauta IH, Muijlwijk T, Leemans CR, van de Ven R. The Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: on Subsets and Subsites. Curr Oncol Rep. 2020 Jun 29;22(8):81. doi: 10.1007/s11912-020-00938-3.

  PMID: 32602047 BACKGROUND

• Echarti A, Hecht M, Buttner-Herold M, Haderlein M, Hartmann A, Fietkau R, Distel L. CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer. Cancers (Basel). 2019 Sep 19;11(9):1398. doi: 10.3390/cancers11091398.

  PMID: 31546872 BACKGROUND

• Rudolf J, Buttner-Herold M, Erlenbach-Wunsch K, Posselt R, Jessberger J, Haderlein M, Hecht M, Hartmann A, Fietkau R, Distel L. Regulatory T cells and cytotoxic T cells close to the epithelial-stromal interface are associated with a favorable prognosis. Oncoimmunology. 2020 Apr 14;9(1):1746149. doi: 10.1080/2162402X.2020.1746149. eCollection 2020.

  PMID: 32363115 BACKGROUND

• Posselt R, Erlenbach-Wunsch K, Haas M, Jessberger J, Buttner-Herold M, Haderlein M, Hecht M, Hartmann A, Fietkau R, Distel LV. Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity. Oncotarget. 2016 Sep 13;7(37):60383-60394. doi: 10.18632/oncotarget.11039.

  PMID: 27494875 BACKGROUND

• Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.

  PMID: 31679945 BACKGROUND

• Wimmer S, Deloch L, Hader M, Derer A, Grottker F, Weissmann T, Hecht M, Gostian AO, Fietkau R, Frey B, Gaipl US. Hypofractionated Radiotherapy Upregulates Several Immune Checkpoint Molecules in Head and Neck Squamous Cell Carcinoma Cells Independently of the HPV Status While ICOS-L Is Upregulated Only on HPV-Positive Cells. Int J Mol Sci. 2021 Aug 24;22(17):9114. doi: 10.3390/ijms22179114.

  PMID: 34502022 BACKGROUND

• Zhou JG, Donaubauer AJ, Frey B, Becker I, Rutzner S, Eckstein M, Sun R, Ma H, Schubert P, Schweizer C, Fietkau R, Deutsch E, Gaipl U, Hecht M. Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors. J Immunother Cancer. 2021 Feb;9(2):e001845. doi: 10.1136/jitc-2020-001845.

  PMID: 33593828 BACKGROUND

• Pages F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, Lugli A, Zlobec I, Rau TT, Berger MD, Nagtegaal ID, Vink-Borger E, Hartmann A, Geppert C, Kolwelter J, Merkel S, Grutzmann R, Van den Eynde M, Jouret-Mourin A, Kartheuser A, Leonard D, Remue C, Wang JY, Bavi P, Roehrl MHA, Ohashi PS, Nguyen LT, Han S, MacGregor HL, Hafezi-Bakhtiari S, Wouters BG, Masucci GV, Andersson EK, Zavadova E, Vocka M, Spacek J, Petruzelka L, Konopasek B, Dundr P, Skalova H, Nemejcova K, Botti G, Tatangelo F, Delrio P, Ciliberto G, Maio M, Laghi L, Grizzi F, Fredriksen T, Buttard B, Angelova M, Vasaturo A, Maby P, Church SE, Angell HK, Lafontaine L, Bruni D, El Sissy C, Haicheur N, Kirilovsky A, Berger A, Lagorce C, Meyers JP, Paustian C, Feng Z, Ballesteros-Merino C, Dijkstra J, van de Water C, van Lent-van Vliet S, Knijn N, Musina AM, Scripcariu DV, Popivanova B, Xu M, Fujita T, Hazama S, Suzuki N, Nagano H, Okuno K, Torigoe T, Sato N, Furuhata T, Takemasa I, Itoh K, Patel PS, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Sargent DJ, Fox BA, Galon J. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018 May 26;391(10135):2128-2139. doi: 10.1016/S0140-6736(18)30789-X. Epub 2018 May 10.

  PMID: 29754777 BACKGROUND

• Driehuis E, Kolders S, Spelier S, Lohmussaar K, Willems SM, Devriese LA, de Bree R, de Ruiter EJ, Korving J, Begthel H, van Es JH, Geurts V, He GW, van Jaarsveld RH, Oka R, Muraro MJ, Vivie J, Zandvliet MMJM, Hendrickx APA, Iakobachvili N, Sridevi P, Kranenburg O, van Boxtel R, Kops GJPL, Tuveson DA, Peters PJ, van Oudenaarden A, Clevers H. Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy. Cancer Discov. 2019 Jul;9(7):852-871. doi: 10.1158/2159-8290.CD-18-1522. Epub 2019 May 3.

  PMID: 31053628 BACKGROUND

• Tanaka N, Osman AA, Takahashi Y, Lindemann A, Patel AA, Zhao M, Takahashi H, Myers JN. Head and neck cancer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity. Oral Oncol. 2018 Dec;87:49-57. doi: 10.1016/j.oraloncology.2018.10.018. Epub 2018 Oct 23.

  PMID: 30527243 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms; Hypopharyngeal Neoplasms; Laryngeal Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms

Study Officials

• Antoniu-Oreste Gostian, PD Dr. med.

  ENT - Head and Neck Surgery Department, University of Erlangen-Nurnberg

  STUDY DIRECTOR

• Markus Hecht, PD Dr. med.

  Radiation Oncology, University of Erlangen-Nurnberg

  STUDY DIRECTOR

• Manuel Weber, PD Dr. med. Dr. med. dent.

  Maxillo-facial-surgery, University of Erlangen-Nurnberg

  PRINCIPAL INVESTIGATOR

• Udo Gaipl, Prof. Dr. rer. nat. habil.

  Translational Radiobiology, University of Erlangen-Nurnberg

  PRINCIPAL INVESTIGATOR

• Benjamin Frey, PD Dr.-Ing. Dr. habil. med.

  Translational Radiobiology, University of Erlangen-Nurnberg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antoniu-Oreste Gostian, PD Dr. med.

CONTACT

+49 9131 85-33156; antoniu-oreste.gostian@uk-erlangen.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2022
• First Posted: May 16, 2022
• Study Start: May 16, 2022
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 17, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

DE (3)